Write-up: This is a spontaneous report from an infectious disease physician. On an unspecified date, the vaccinee received the second dose of Lymerix. The vaccinee subsequently, experienced optic neuritis. Physician stated that at this time is was not clear whether the pt developed multiple sclerosis or if this could be adverse effect of the vaccine. This case is considered to be medically serious. The most recent information, received on 4/19/2000, reports the condition of the pt is unknown. Request for additional information has been forwarded to the primary care physician. Follow-up states that this report describes multiple sclerosis in a 33 male who received Lyme disease vaccine recombinant. Additional info was received via the litigation process. Medical history included "life-long" depression, anxiety, unspecified speech impediment for which he received speech therapy, allergies to pollen and mold, allergic rhinitis, rustachian tube dysfunction, chronic serous otitis media, low blood pressure, prostatitis, fatigue, and chronic bilateral knee pain. Following the reported onset of the multiple sclerosis, the vaccinee experienced bursitis of the right heel, tendonits/bursitis of the right shoulder after a fall from ten foot, acute pharyngitis/bronchitis, otitis media and externa sinusitis, urinary tranct infection caused by escherichia coli, chest pain, and cholelithiasis. These were not reported as adverse events due to vaccine administration, but were found during the course of review of the vaccinee''s medical records. Therefore, they are not listed as adverse events. He reports bilateral knee pain, left being worse. He''s had his parin for two years; however, he feels it became worse a month after he received his second LYMErix. The vaccinee returned to the physician''s office on 11/24/1999 with chief complaints of "possible sinus infection, cough." The vaccinee also wanted the physician "to recheck his knee. He''s continuing to have locking and extreme stiffness when he gets down to do any filing. he''s unable to straighten the knee for any period of time." The physician prescirbed Ceftin to treat the sinusitis and bronchitis. The sinutitis/bronchitis also resolved. On 01/07/2000, the pt presented to his primary care provider with a chief complaint of eye pain of three days'' duration. The vaccinee seen by the ophthalmologist on 01/07/2000. He was prescribed Keflex for seven days. The ophthalmologist saw the vaccinee again on 01/10/2000. At that time, he reported "severe pain on left eye started Sunday morning. Left eye has dark sports and the rest is cloudy. It has a gray tint like looking through." The ophthalmologist recorded current medication as azithromycin. The ophthalmologist wrote, "left optic neuritis-need to rule out Lymes." The vaccinee was referred to a neurologist, who saw him on 01/27/2000. The neurologist''s improssion is that the vaccinee is suffering form eigher a idiopathic viral optic neuritis or possibly Lyme optic neuritis. The vaccinee was seen by the infectious disease specialist on 02/10/2000. The specialist wrote,"the differential diagnosis included normal variant vasculitis, Lyme disease or multiple sclerosis. The vaccinee returned to the neurologist on 04/27/2000. The neurologist wrote, " I think that he probably has MS, particularly with this new symptom of Lhermitte''s sign." The vaccinee underwent MRI of the brain, without contrast. The vaccinee presented to his primary physician on 10/14/2000 complaining of pain in both knees. The vaccinee returned to his first neurologist on 02/07/2001. The Avonex therapy was continued. The most recent info received on 01/11/2002, indicated that the optic neuritis resolved with sequelae. Lhermitte''s sign persisted as of 02/07/2001. The chondromalacia patellae, sinusitis, and bronchitis had resolved without sequelae. On 02/11/2002, in a statement of injuries, the vaccinee''s attorney alleged that the vaccinee "has been diagnosed with optic neuritis which, after causing total blindness in his left eye for four months, has resulted in a 50% vision loss in his left eye. In addition he suffers from fatigue, and has suffered joint pain in his left knee, a tingling sensation in his left arm and left leg, and burning pains in his right hip, knee and ankle. The most recent info received on 02/11/2002 did not specify the outcomes of the reported events, except that the vaccinee contnued to experience 50% vision loss in his left eye. Multiple sclerosis is considered medically serious. Reported on 03/26/2003: "Medical history included "life-ling" depression, anxiety, unspecified speech impediment for which he received speech therapy, granulomatous lung diseaase, allergies to pollen and mold, chronic cough, perennial allergic rhinitis chronic sinusitis (1998), Eustachien tube dysfunction, chronic srious otitis media, labrynthitis (1997), low blood pressure, sinus bradycardia, premature ventricular contractions, prostatisis (1996), bladder outlet obstruction (1998), fatigue (1995), and chronic bilateral knee pain (1997). The vaccinee reportedly had no clinical history of Lyme disease. A pre-immunization Lyme ELISA was reportedly positive, but the Western blot was negative (NDA). The vaccinee reportedly had no known family history of auteimmune of collagen vascular disease. However, a "distant cousin" had multiple sclerosis, and the vaccinee''s uncle "had similar presentation" of acute visual chages during an episode of sinusitis. Concurrent medications included alprezolam, lorenspam, buspirone (BusPar), fluoxetine (Prozac), paraxetinc (Paxil_), sertraline (Zoloft), trazodone, fexofenadine/pseudoephedrine (Allegra-B), loratadine/pseudoephedrine (Claritin-D), and allergy hyposensitization shots to mold, grass, and ragweed commencing September 1998 and continuing through at least November 2002. Following the reported onset of the multiple sclerosis, the vaccinee experienced bursitis of the right hell, tendonitis/bursitis of the right shoulder after a fall from ten feet, acute pharyngitis/bronchitis, otitis media and externa, sinusitis, urinary tract infection caused by Escherichia coli, chest pain, and cholelithiasis. These were not reported as adverse events due to vaccine administration, but were found during the course of review of the vaccinee''s medical records. Therefore, they are not listed as adverse events. On 08/24/1999, the vaccinee received the first injection of LYMErix. No adverse events were reported following this injection. ON 09/21/1999, the vaccinee received his second injection of LYMErix (lot LY123B9). The vaccinee presented to his physician on 10/25/1999 "with multiple complaints. He reports bilateral knee pain, left being worse. He''s had this pain for two years; however he feels it became worse a month after he received his second LYMErix vaccine. He denies any recent trauma or injury. He also reports he''s had some swollen glands and a scratchy throat for the past two to three days. He did just recently go on a scuba diving and he thinks the symptoms worsened since then. Other family members are home ill with the same thing." On physical examination, "TMe (tympanic membranes) are clear and patent bilaterally with very minimal aerous changes on the right. Nose, very minimal swelling of the turbinates, no drainage or discharge noted. There is some palpable cervical lymphadernopathy. Throat, without evidence of infection...Exam of the knee-there is no evidence of affusion in either knee. He does indicate that the pain is under his knee-cap and does increase when he is squatting or on his knees. He denies any locking or giving out of the knees. Anterior and posterior draw is negative. Laehman''s maneuver is negative. He''s got good ROM (range of motion). There is no crepitance felt...He denies any associated swelling or the knee feeling warm or hot. He denies any fevers associated with this." The physician''s diagnosis were "Chondromalgia bilaterally, Sinusitis, Depression." The physician prescribed cephaloxin5000mg three times daily for ten days to treat the sinusitis. The physician reported that the sinusitis resolved and was not incapacitating. The vaccinee returned to the physician''s office on 11/24/1999 with chief complaints of "possible sinus infection, cough". the vaccinee also wanted the physician "to recheck his knee. He''s continuing to have locking and extreme stiffness when he gets down to do any filing. He''s unable to straighten the knee for any period of time." On physical examination, the "TMs are slightlydull but not erythematous. Throat is erythematous. he has some frontal and maxillary sinus tenderness to palpation....Lungs are essentially clear at the bases. I also happened to notice the patient has a slightly orangish skin tone. He does admit to eating four to five small carrots at breakfast every morning. he does this to try to keep his weight down...he does appear to have some laterol joint line tenderness, increased pain in flexion and extension, small amount of effusion." The physician''s assessment was "Sinusitis, Bronchitis. I feel he has a mild carotinemia from the daily carrot intake. Internal derangement of left knee." the physician prescribed ceforoxime (Ceftin) to treat the sinusitis and physician reported that teh knee pain resolved spontaneously, and was not incapacitating. The sinusitis/bronchitis also resolved. On 01/07/2000, the patient presented to his primary care provider with a chief complaint of eye pain of three days duration. "He''s complaining of pain behind his left eye. Pain when he moves his eye and like a cloud over his left eye." Fundoscopic examination was "normal. I found no evidence of papilledema or glaucoma. Floureescain staining negative." The vaccinee was referred to an ophthamologist. The vaccinee was seen by the opthalmologist on 01/07/2000. He reported "Tuesday morning OS (left eye) felt like the muscles were strained...Feels like pressure OS. Things have a gray tint with OS." Visual acuity was 20/20 in both eyes. The ophthalmologist''s impression was "sinusitis". She prescribed cephalexin (Keflex) 500mg four times daily for seven days. The opthalmologist saw the vaccinee again on 01/10/2000. At that time, he reported "Severe pain OS started Sunday morning. OS has dark spots and the rest is cloudy. It has a gray tint like leaking through ''fog''." The ophthalmologist recorded current medication as azithromycin (Z-Pac). Visual acuity was 20/20 in the right eye and 20/30 in the left eye. Red desaturation in the left eye had dropped to 15%. The opthalmologist''s impression was ''Left optic neuritis. Reckbeck Lyme titor. Got Lyme vaccine in September." On 01/13/2000, total Lyme antibodies were positive; Western blot analyses for Lyme IgG and IgM were negative. Antinuclear, antibody (ANA) titer was negative. On 01/17/2000, visual acuity in the vaccinee''s left eye was 20/80. There was a "definite" afferent pupillary defect in the left eye. Result of a Humphrey visual field test "was consistent with an enlargement of a blind spot OS." The opthalmologist wrote, ''Left optic neuritis - need to rule out Lyme (sic)." X-ray of the eyes was performed on 01/26/2000. The radiologist reported, "Views of the orbits fail to demonstrate a persistent metallic foreign body within the orbits. There is a tiny metallic density seen within or about the maxillary sinus. The bones are normally mineralized." MRI of the brain (with and without contrast) was also performed on 01/6/2000. The radiologist''s impression were 1. Findings compatible with left optic neuritis. 2. A single focus of deep white matter disease in the left periventricular area, a nonspecific finding. 3. Mucous retention cyst at the floor of the left maxillary sinus." The vaccinee was referred to a neurologist, who saw him on 01/27/2000. At that time, the vaccinee was "also complaining of some intermittent heart beat and some joint pains. He has not had any rashes. he denies any headaches. he had visual fields done which showed, loss of vision in the left eye. he now states that the pain is gone and he is starting to get return of vision of the left eye." On physical examination, "His left optic nerve appears a bit full but there is no frank edema." The neurologist wrote,"His MRI showed some swelling and enhancement in the left optic nerve and one high signal in the white matter which was not involving the corpus callosum. IMPRESSION: I feel that the patient is suffering from either a idiopathic viral optic neuritis or possibly Lyme optic neuritis." The vaccinee was referred to an infectious disease specialist. The vaccinee was seen by the infectious disease specialist on 02/10/2000. The specialist wrote, "The differential diagnoses included normal varient visoulitis. Lyme disease or multiple sclerosis. he has not really had any other neurologic symptoms and may be having some diplopia. He does not stiffness in his left knee, but no frank orthrisis. It only bothers him when no stoops down and then tries to get up. he also has some stiffness and pain in his fingers at times. He does note increasing fatigue, occasional papitations. No frank myalgies. he has never had erythema migraine type rash....No were asked to see him regarding the question of Lyme disease." The specialist noted, "he does spend a lot of time outdoors and does have a hisory or tick exposures." The assessment was "Optic neuritis, question infectious etipology , for example Lyme, syphilis, other infections in the differential diagnoses would be tuberculosis, eat scratch disease, toxoplasmosis or post Varicella herpes simplex virus. Mycoplasma, or Epsetin-Barr virus. Certainly multiple sclerosis is very high in the differential diagnoses or collagen vasular disease, such as lupus erythematosus or post immunization adverse event." total Lyme antibodies were positive. Lyme IgG by Western blot analysis was negative, with only a 30 kD band present. The laboratory report contained the following note. "Results for the Lyme Western Blot do not meet the CDC/ASTPHLD Criteria for classification as Positive. However, strong reactivity, which is largely restricted to OspA (p31) is present. This pattern can often be found in response to vaccination." Lyme IgM by Western blot analysis was negative. Rheumatoid factor was negative. The vaccinee was seen by the opthalmologist on 02/16/2000. "His vision had improved to 20/50 OS....His color vision was greatly diminished OS and he could only identify 2 out of 13 color plates. A repeat visual field test showed a dramatic improvement in his field OS, although there is some central ecotoma." The vaccinee underwent lumbar puncture on 02/21/2000. Cerbroxpinal fluid (CSP) protein was elevated, as more red blood cells, white blood cells, lymphocytes, IgG index, IgG/total protein ratio and IgG synthesis rate. Stain for acid fast bacilla (AFD) was negative. VDRL was non-reative. Lyme IgG was not detected in the CSF, Lyme DNA was also not detected in CSF by polymerase chain reaction 9PCR). The vaccinee was seen by his allergist on 03/04/2000. At that time, the subject reported that he had developed optic neuritis with protein in his cerebrospinal fluid. The question was raised regarding a relationship with the hyposensitization shots the subject was receiving. The allergist wrote, "I don''t think so." The opthalmologist saw the vaccinee on 04/24/2000. At that time, the vaccinee reported leg numbness and weakness. Visual acuity in the left eye was 20/20, and the vaccinee correctly identified 6 out of 13 color plates. The opthalmologist wrote, "In summary the vaccinee continues to show improvement which is steady...he recognizes that his contrast sensitivity will not be quite as it had been prior to this event." The vaccinee returned to the neurologist on 04/27/2000. The neurologist wrote, "I think that he probably has MS (multiple sclerosis). Interestingly he recently had an attack of left leg numbness and he does describe Lhermitte''s sign. His physical examination today fails to show any focal findings, although his reflexes are a bit brisk. IMPRESSION: as before I still think that all this is MS, particularly with this new symptom of Lhermitte''s sign." The vaccinee underwent MRI of the brain, without contrast, on 05/08/2000. Under clinical information, the radiologist noted "Tingling in the left arm and leg. Optic neuritis in the left eye. Headaches and blurred vision." The radiologist''s impressions were "1. No evidence of intracranial mass or mass effect. 2. Small hyperintense single focus right posterior periventricular region which is nonspecific. No other evidence of demyalinating plaques. 3. Hatention cyst in the left maxillary antrum" The vaccinee also underwent MRI of the cervial spine. The radiologist''s impression was "No evidence of disc herniation, spinal stenosis, or definite evidence of cervical cord demyslinating plaques." The vaccinee saw his primary physician on 08/17/2000. "He is in to say that he has seen (the opthalmologist). His vision he said in the involved eye is 50%. Originally he was seen here last fall with left knee pain. He now has at times pain in his right leg around the right hip, sometimes the right knee....He is seeing his neurologist who continues him on Avonex with the diagnosis of KS." The physician noted that a test for HLA-DR4 antigen, performed 08/04/2000, was positive. On physical examination, there is no overt swelling. He does have full ROM. There is no muscle wasting. I do not detect a rash." The diagnoses were recorded as "right leg pain, left optic neuritis." On 08/19/2000, antinuclear antibody titer was negative and erythrocyte sedimentation rate was 0mm/hr. The vaccinee was seen by a neurologist at a care center on 09/06/2000 "for evaluation for possible multiple sclerosis and previous history of optic neuritis." The neurologist wrote, "By 04/14/00, the patient started experiencing some episodic tingling effecting mostly the left lower extremity which was triggered by movement of his head, particularly when he was flexing his head. This symptomatology persisted for the next two months and has improved over the past several weeks. During the summer, he experienced some right hip, knee and ankle discomfort triggered by leg movement. He also has experienced some burning sensations effecting the external aspect of his right kneecap." This neurologist noted that Avonex therapy began on 04/24/2000. "One of the main reasons this consulation was generated, in associated concerns that the patient has about the potential effect of the Lyme disease vaccination that he received last year....The main question is if the Lyme disease vaccine is associated with the multiple sclerosis." The neurologist noted that the vaccinee had a "distant cousin" with multiple sclerosis. Review of symptoms "is characterised by a patient who has problems with insomnia and has increased fatigaility. He reported the presence of joint pain and symptomatology associated with anxiety and depression." Under "major findings", the neurologist recorded, "There was no evidence of nystegmus; however, there was evidence of what appeared to be mildly atexic pursuit. The pupils appeared slightly asymetric with the left pupil smaller when compared to the right pupil, but the photo reaction was quite active in both pupils. There was no clear but evidence of afferent pupillary defect....I had the opportunity to review the magnetic resonance of the brain obtained in 05/00 that revealed minimal changes particularly affecting a deep area in the midbrain and the right aspect with increased signal intensity in the T2 sequence. This area is small and rounded with no mass effect. There is a second area in the loft subcortical region of the cingulate gyrus in the frontal lob that also appeared to have a T2 hyperintensity and was also tetected in the flare sequence." The neurologist''s assessment was "At this moment, we are quite sure that the patient''s major neurologic problem has been the presence of optic neuritis. It is likely that this situation is associated with multiple sclerosis; however, at this moment there is no clear indication that there are other areas of white matter involvment producing symptomatologies. The MRI demonstration of minimal white matter changes may suggest that the likelihood of multiple sclerosis or the severity of multiple sclerosis may be low in his case. This is based on previoius epidemiological studies. The main question is whether the problem of optic neuritis is associated wih the vaccination or just a minifestation of MS....There is no clear epidemiological demonstration of a link between opitic neuritis. Multiple sclerosis with the Lyme disease vaccination....I explained this to the patient. I emphasized that if there is any link, there is no clear cut demonstration at this moment." The diagnoses were recorded as "1. left optic neuritis (1-2000). 2. Possible multiple sclerosis. 3. Previous history of Lyme disease vaccination." The vacinee presented to his primary physician n 10/16/2000 "complaining of pain in both knees." Physical examination revealed "tenderness in the medial aspect of both joints. Negative Lachman''s, negative drawer''s, +/- McMurray''s, nothing definitive. Tenderness when moving the petella superiorly inferiorly bilaterally." His assessment was "bilateral chondromalacia patella with effusion and strain of knees." The physician injected each knee joint with a combination of traincinolone, dexanothasone, and lidocaine. He also prescribed neproxen. On 10/30/2000, the physician prescribed rofecoxib. The vaccinee returned to his first neurologist on 02/07/2001. The neurologist wrote, "He is doing well. He still gets his Lhermitte''s sign and his vision never came totally back. Overall, he is doing well." Avonex therapy was continued. The vaccinee underwent MRI of the brain (with and without contrast) on 05/29/2001. The radiologist''s impression was "Single tiny focus of bright signal in the posterior left periventricular white matter. This is non-specific and comparison with prior studies would be recommended when they can be made available. No other intracranial abnormalities are noted." The vaccinee returned to his second neurologist on 07/11/2001. The neurologist noted, "He has continued with normal life with no evidence of major neurological problems or symptoms....The main question for this visit is if he can stop Avonex". On examination, "His neurological examination is really fine except for some areas of abnormalitites in extraocular movements and fundoscopic examination. The left optic nerve shows some evidence of pallor, but the retina and blood vessels appear find. The extraocular movements indicate that there is a full range of movement with some end gaze nystagmus, and occasionally there is some staxic pursuit." The neurologist''s assessment was "The vaccinee is doing fine after his episode of optic neuritis. The the moment, the neurologic examination is completely unremarkable, and there is no radiological areas of any demyelinating plaque of any abnormality that suggests that this is progressing." His diagnoses were "1. Left optic neuritis, 1/00. 2. Previous history of Lyme disease vaccination." On 02/11/2002, in a statement of injuries, the vaccinee''s attorney alleged that the vaccinee ''has been diagnosed with optic neuritis which, after causing total blindness in his left eye for four months, has resulted in a 50% vision loss in his left eye. In addition, the patient suffers from fatigue, and has suffered joint pain in his left knee a tingling sensation in his left arm and left leg, and burning pains in his right hip, knee and ankle. The subject returned to his allergist on 11/01/2002. He reported that during the "End of September lot of sinus infections." He had previously reported (10/10/2000) that his "worst months" for allergy sumptoms were September and October. At the 11/01/2002 visit, the subject also reported that his second neurologist "thinks optic neuritis secondary to LYMErix vaccine, unlikely MS (multiple sclerosis) so off Avonex." The vaccinee reported that he began to experience fluid in his ears, nasal congestion, post-nasal drainage, and cough in mid-August to September. On physical examination, the nasal membrance were moderetely boggy. The allergist''s assessments were chronic sinusitis, pernnial allergic rhinitis, chronic cough, and Eustachian tube dysfunction. He prescribed fluticasone nasal spary and cetirizine. The most recent information recieved on 03/18/2003, did not specify the outcomes of the reported events. Information received on 02/11/2002 indicated that the vaccinee continued to experience 50% vision less in his left eye. Medical recordss received on 01/11/2002 indicated that the optic neuritis resolved with sequelac. Lhermitte''s sign persisted as of 02/07/2001. The chondromalacia patellao, sinusitis, and bronchitis had resolved without sequelac. Multiple sclerosis is considered medically serious (OMIC). Follow up on 03/24/04 states: "The most recent information, received on 03/14/04, did not specify the outcome of the reported events. Information received on 02/11/02 indicated that the vaccinee continued to experience 50% vision loss in his left eye. Medical records received on 01/11/02 indicated that the optic neuritis resolved with sequelae. Lhermitte''s sign persisted as of 02/07/01. The chondromalacia patellae, sinusitis, and bronchitis had resolved without sequelae. Multiple sclerosis is considered manufacturer''s medically serious." Follow up on 07/15/04 states: " The most recent information, received on 07/01/04, did not specify the outcomes of the reported events. Information received on 02/11/02 indicated that the vaccinee continued to experience 50% vision loss in his left eye. Medical records received on 01/11/02 indicated that the optic neuritis resolved with sequelae. Lhermitte''s sign persisted as of 02/07/01. The chondromalacia patellae, sinusitis, and bronchitis had resolved without sequelae. Optic neuritis is considered manufacturer medically serious (OMIC)."

Write-up: In April, 1999, the pt received her first injection of Lymerix, with no side effects. In May, 1999, she received the second dose and the frequency of her arthralgias seemed to lessen. Approximately 5 months later, October, 1999, he arthralgias increased, and she went to a rheumatologist. She was found to have an elevated erythrocyte sedimentation rate, and on 10/25/1999 was diagnosed with Waldenstroms macroglobulinomia. She was hospitalized in late November 1999 and received chemotherapy for one week. She again was hospitalized on 1/7/00 and received another week of chemotherapy. The information received on 4/27/00 provides no further information.

Write-up: In early April, 1999, the pt received her first treatment with Lymerix at an unspecified dose for prophylaxis. Approximately two weeks later, she found out that she was pregnant. She became pregnant approximately late February or early March 1999, and her last menstrual period was mid to late February, 1999. The pt had an uncomplicated prenatal course. Because of failure to progress to labor and term, the child was delivered by cesarean section on 12/16/1999. The newborn was viable and had no anomalies during the newborn exam. At the childs 2 week check up it was doing quite well. There were no complications during pregnancy and no obvious anomalies to the newborn.